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A head full of horrors

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Medicine throws a cocktail of drugs at migraine, with questionable benefits, when many practitioners have proved that a change of diet can often cure it forever

Medicine throws a cocktail of drugs at migraine, with questionable benefits, when many practitioners have proved that a change of diet can often cure it forever.

Despite an estimated one in 10 people suffering from migraine, no one really knows what causes it, or how to cure or prevent it. This adds up to a catalogue of heavy duty drugs being administered in a hit and miss fashion to treat a condition no one knows much about, despite the fact that there is evidence of a much simpler, safer and, it seems, more effective form of treatment.

Analgesics, including aspirin, paracetamol and codeine, are sometimes combined with a drug called metoclopramide to speed the absorption and enhance the effectiveness of the analgesics. But metoclopramide can cause dystonia, a condition characterized by muscle rigidity, spasms, unusually fixed postures or strange movements. If nausea and vomiting are part of the migraine pattern, analgesics may be combined with anti-nausea drugs, such as perphenazine, prochlorperazine and chlorpromazine. These drugs occasionally cause tardrive dyskinesia, characterized by irreversible twitching, jerking or writhing.

Ergotamine and dihydroergota mine, both 5-HT agonists which reduce swollen blood vessels around the brain, are now favoured migraine drugs. Amongst migraine sufferers taking dihydroergotamine, there have been 18 reported cases of heart attack, three resulting in death. Only two of the patients had a history of heart disease, and 78 per cent had no risk factors for ischemic (reduced blood flow) heart disease. Other possible side effects include nausea, vomiting, abdominal pain, diarrhea, muscle cramps and partial paralysis or muscle weakness.

Sumatriptan is perhaps the best known of the 5-HT agonists. When it was launched in the early 1990s, it was hailed as the most successful migraine medical treatment to date. In two placebo controlled trials which included 1600 migraine sufferers, between 81 and 86 per cent had their headaches reduced from moderate or severe to mild, or none, within two hours. (N Engl J Med, 1991; 325:316-21 and JAMA, 1991; 265:2831-5). However, in another trial, up to 40 per cent of patients whose headaches were reduced by a single dose of sumatriptan experienced recurrent headaches, which were not prevented by repeated doses of the drug (Eur Neurol 1991; 31:306-13).

More recent studies have shown that at least 5 per cent of sumatriptan users experience chest pains similar to those associated with angina. These are probably due to the drug's vasoconstrictive effect; it narrows blood vessels and restricts blood flow. One 47 year old woman with no previous history of cardiovascular disease suffered a fatal heart attack after injecting herself with sumatriptan (The Lancet, 1993; 341: 861-2), and two patients developed serious irregular heartbeats (BMJ, September 19, 1992). The drug may also cause a rise in blood pressure, and researchers have found that some patients taking sumatriptan suffer from increasing recurrences of migraine. In addition, there is evidence of possible dependence on the drug. (For more information on sumatriptan, see WDDTY, vol.5, no.10, p 8-10.)

There have been several comparisons made between sumatriptan and other anti-migraine therapies. When compared with a combination of ergotamine and caffeine (Cafergot), sumatriptan was significantly more effective at reducing the intensity of headache (66 vs 48 per cent). However, migraine recurrence was more common amongst those patients taking sumatriptan than those taking ergotamine/caffeine (Eur Neurol, 1991; 31:314-22).

Nonsteroidal anti-inflammatory drugs (NSAIDs) are favoured for patients with mild to moderately severe migraine attacks, and these are also sometimes combined with metoclopramide. In addition, patients may be switched haphazardly from one to the other NSAID in an effort to find one that works for them.

Both the NSAIDs and 5-HT agonist drugs are also used preventatively, with limited success. In one trial naproxen, a NSAID, only prevented half the patients (52 per cent) from developing severe headaches, although all patients receiving the drug found that the severity and duration of headaches, the frequency of nausea and vomiting, and the use of analgesic medication were all reduced (Neurology, 1985; 35:1304-10). However, it is recommended that NSAIDs are not used for prolonged periods, due to the risk of gastrointestinal ulceration and bleeding which effectively negates their prophylactic role.

Of the 5-HT agonist drugs, those considered to be the most effective are methysergide and amitriptyline, but again both have worrying side effects. Long term treatment with methysergide can cause fibrosis, such as inflammation and scarring of tissue of the lungs, heart valves and ureters (tubes which carry urine from the kidneys to the bladder), possibly resulting in organ failure. Amitriptyline can cause weight gain, drowsiness, blurred vision and irregular heartbeat.

At the other end of the scale, we have calcium channel blocking drugs which are used to prevent migraine, although overall their effect has been unimpressive. They have the opposite effect to the 5-HT agonists, in that they cause "vasodilation", increasing blood flow by widening blood vessels. For this reason they are often used to treat angina and heart arrhythmias.

However, although they may decrease the frequency of migraine attack, they seem to have little effect on severity and have even been known to bring on headaches that are so severe they are indistinguishable from migraines! (N Engl J of Med, 1993; 329 (20):1481.)

Then there's sodium valproate, a drug more commonly used to treat epilepsy. This has been shown to be moderately effective in preventing migraine and reducing the frequency, severity and duration of severe attack, although it's not really known why this should be so (Cephalalgia, 1992; 12:81-4). And yet again there are some serious side effects including hair loss, weight gain, potentially fatal liver problems and neural tube defects in fetuses.

Danazol is a drug commonly used to treat endometriosis, yet despite some very disturbing side effects may also be used to prevent hormonally related migraines. One study found that out of 131 women with hormonally related migraines that had not responded to standard medication, half experienced profound relief after a year.

But what danazol actually does is induce a post-menopausal state including all the usual side effects.

Tamoxifen, a drug used in the prevention and treatment of breast cancer, is also reported to be effective in preventing hormonally related migraines (The Lancet, 1986; 2: 1344).

However, the side effects and risks associated with this drug are enough to make even those with breast cancer think twice about taking it. Tamoxifen increases the risk of endometrial cancer about five fold (The Lancet, 11 January 1992), and tamoxifen patients have experienced abnormal vaginal bleeding, hyperplasia (excessive cell formation) polyps and endometriosis (BMJ, October 26, 1991).

Tamoxifen has been associated with seven times the risk of thrombosis of the veins or arteries (J of Clin Onc, 1991; 9:286-94.) It has also been linked with toxic effects on the eyes, (BMJ, 1992; 304:495-96), with an estimated incidence of 6.3 per cent, and may cause liver damage, including cancer.

According to research quoted in allergist and WDDTY panellist Dr John Mansfield's The Migraine Revolution (Thorsons), food allergy is the main single cause of migraine and accounts for between 80-90 per cent of the problem.

The most comprehensive, double blind controlled trial of food allergy and migraine to date, conducted by the Department of Neurology and Immunology at the Hospital for Sick Children (Great Ormond Street) and the Institute of Child Health, found that 93 per cent of 88 children with severe, frequent migraine recovered once the foods they were allergic to had been detected and eliminated from their diet (The Lancet, October 15, 1983).

Dr Mansfield also says that, contrary to the popular belief that foodstuffs such as cheese, chocolate and red wine are most likely to trigger migraine, wheat, corn, milk, sugars and oranges are the biggest offenders.

In fact, WDDTY panel member Dr Melvyn R. Werbach, assistant clinical professor at UCLA's School of Medicine, has found evidence both for and against the link between chocolate and migraine. In one controlled study, 36 patients who attributed their migraines to chocolate were given either phenylethylamine or placebo. Phenylethylamine is a vasoactive amine capable of changing the size of blood vessels, which is found in chocolate. All 18 patients in the phenylethylamine group reported attacks 12 hours after taking phenylethylamine, compared to six of the 18 who took the placebo (Nature 1975, 257:256).

In another double blind study, 13 out of 80 patients had a migraine attack after eating chocolate, but in only two could these reactions be reproduced with consistency (J Neurol Neurosurg Psychiatry, 1974; 37:445). And in another double blind study, 100 patients showed no evidence of an increase in frequency of headaches after taking tyramine (another vasoactive amine found in chocolate), phenylethylamine or chocolate, despite their conviction that chocolate would cause them to develop a headache (The Lancet 1974; 2:7885).

Dietary copper may trigger migraine. Copper is involved in the metabolism of the vasoactive amines, and Dr Werbach believes that this metabolic process may be abnormal in migraine sufferers. Foods with a high copper content include chocolate, nuts, shellfish and wheatgerm. Citrus fruits increase intestinal copper absorption, and monosodium glutamate (MSG) binds and transports it. Both citrus fruits and MSG have been linked with migraine.

Other studies suggest that supplementation with vitamin B6, magnesium, lithium and/or omega-3 fatty acids (fish oils) may help relieve migraine symptoms. In one double blind study, 15 patients who had severe migraine which hadn't responded to medication found they were having fewer headaches, which were not as intense, after taking supplements of fish oils EPA (eicosapentaenoic acid) and DHA (docosahexaenoic acid) (Am J Clin Nutr 1986; 43:710). Cod liver oil is not recommended due to its high vitamin A content.

In another double blind study, six chronic sufferers with severe, very frequent migraine were given 20mg of fish oil or placebo daily for two six week treatment phases. Five patients experienced significant relief, of both frequency and intensity of headaches (Am J Clin Nutr, 1985; 41:874a).

Although both men and women can develop migraine as a result of low magnesium, women are especially prone to this type of migraine during periods and the latter part of pregnancy. In one study, 80 per cent of a group of 3000 women appeared to have a good response to magnesium supplements. Dr Werbach recommends combining a magnesium supplement with vitamin B6 to help raise magnesium levels and make it more effective.